Specific goals for the coming year arise from the objectives expressed under IIIA above, and they reflect the specific aims that were outlined in the latest application for competitive renewal of this grant: (a) to isolate and charaterize neurohypophysical presursor molecules from extract of 14,000 rat posterior pituitary glands; (b) to measure the production of ADH during postnatal development of rats, as well as the renal handling of urea during this period; (c) to assess the water permeablility of collecting duct luminal membranes through aggregation of intramembranous particles, in: (1) dehydrated Brattleboro homozygotes and dehydrated normal rats, (2) normal rats during the first, second, fifth, and tenth postnatal weeks, and (3) mice with hereditary nephrogenic diabetes insipidus (D.I.); (d) to further define our model of mice with hereditary nephrogennic D.I. by: (1) measuring their production of neurohypophysical principles, (2) examining their VP-and OT- producing neurons through immunohistochemical techniques, and (3) examining vasopressinergic neurons in the extrahypothalamic system by the same techniques; (e) to define the kind of D.I. in guinea pigs with hereditary D.I. that are now being bred by us; (f) to further investigate possible mechanisms that lead to concentration of urine in the absence of ADH; and (g) to explore the mechanisms that alter renal function during anesthesia and surgery.